HIV is the leading cause of death in adolescent girls and young women (AGYW) aged 15-24 years. Despite advances in HIV treatment and prevention, AGYW remain at high risk, particularly in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) is highly effective and has the potential to make a dramatic impact on the HIV epidemic. Yet to date, most trials of PrEP in women have been unable to demonstrate efficacy, largely due to poor adherence among AGYW. Emerging evidence indicates that women may be more likely to use an HIV prevention method that also prevents pregnancy. We will test an intervention consisting of a single oral capsule providing both PrEP and contraception ? a contraceptive multipurpose prevention technology (cMPT) ? as a strategy for increasing PrEP adherence compared to oral PrEP alone. We will enroll AGYW who already use a COCs in Harare, Zimbabwe, where AGYW continue to be at high risk of HIV, more than half of contracepting women use COCs, and less than 1% of 15-35-year-old women are using PrEP. The cMPT intervention will contain two marketed products: Truvada [emtricitabine and tenofovir disoproxil fumarate (TDF)] and a combined oral contraceptive (COC) [levonorgestrel (LNG)/ethinyl estradiol (EE)]. This research will implemented through a collaboration between the Population Council, which has global expertise in clinical trial, implementation science, feasibility studies and evaluation around female-initiated HIV prevention methods, and the University of Zimbabwe College of Health Sciences (UZCHS), which has a long history of conducting HIV clinical studies and prevention research. In Aim 1, we will conduct qualitative formative research to explore the acceptability of combining Truvada with a COC to increase PrEP adherence through focus group discussions with AGYW and in-depth interviews (IDIs) with healthcare providers. In Aim 2, we will incorporate formative research findings into the development and pre-testing of 1) cMPT packaging and client information materials; 2) adherence and acceptability questionnaires; and 3) a provider training manual. In Aim 3, we will compare the acceptability, preference, and adherence of the cMPT intervention versus standard of care (2 separate pills: Truvada and COC). In a 6-month randomized, crossover study, 30 AGYW (16-24 years old) in Harare, Zimbabwe will be assigned in random order to the sequence of the 2 regimens: the cMPT intervention or standard of care (2 separate pills). Each regimen will be used for 3 28-day menstrual cycles (approximately 3 months per regimen). At the end of 6 months, women will be asked to state their preference for the cMPT intervention or the 2 separate pills. We will assess and compare acceptability and adherence (via dried blood spots) of the 2 regimens, and socioecological factors (e.g., individual-, partner-, family-, clinic-level) associated with adherence and acceptability. We will explore facilitators and barriers to use through IDIs with 5 AGYW who complete the study and all AGYW who withdraw early. Acquiring confirmation now on the preference for an oral cMPT from actual use with currently approved products will accelerate the availability of such a product in the marketplace. Given supportive findings in this project, we will outline a process for regulatory approval of the more cost- effective co-formulated pill.